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Particle sizing and biokinetics of interstitial lymphoscintigraphic agents.

The biokinetics of inert lymphoscintigraphic agents strongly depends on their particle size. Different techniques for characterization of colloids are discussed. Experiments have been performed on eight different colloids. The particle size has been investigated with scanning electron microscopy. Activity distributions have been obtained with ultrafiltration and gel-column scanning technique. The colloids suggested for lymphoscintigraphy were found to have a median size of about 40-50 nm except one minimicro-aggregated human serum albumin colloid which has a median particle size around 10 nm. The biokinetics were studied with a scintillation camera in rabbits after a subcutaneous injection. Time-activity curves were generated. After 5 hr the rabbits were dissected and the activity content in different tissues measured. A compartment model for the biokinetics was designed and rate constants evaluated. The total and specific activity uptake in parasternal lymph nodes was highest for the small-particle colloids. The compartment model showed a good fitting to the experimental data.

Absorption↗

Effect of compaction on particle size.

Compressed tablets were prepared on a hydraulic press at several different compaction pressures by a standardized technique, using aspirin, dicalcium phosphate dihydrate, calcium phosphato-carbonate, alumina, and microcrystalline cellulose. All tablets except microcrystalline cellulose contained a cation-exchange resin as disintegrant. The particle-size spectra of the disintegrating compacts were evaluated using a particle-size counter or an air jet sieve. It is shown that compacts made from different materials but of the same initial particle-size spectra disintegrate to give particles of a considerably different size. Determination of the change in particle size produced by the compaction process provides useful insight into the nature of the compaction process.

Aluminum↗

Influence of the particle size on the adjuvant effect of particulate polymeric adjuvants.

The influence of the particle size of poly(methyl methacrylate) and polystyrene particles on the adjuvant effect of model vaccines was investigated in mice using bovine serum albumin as the antigen. The particle sizes of the adjuvants were between 62 and 306 nm. Smaller particles yielded a much better adjuvant effect than bigger particles. The adjuvant effect of the small polymer particles was better than that of 0.2% Al(OH)3. All adjuvants yielded a higher antibody response than the fluid antigen preparation.

Adjuvants, Immunologic↗

Influence of particle size and dissolution conditions on the degradation properties of polylactide-co-glycolide particles.

Polymer degradation usually plays a crucial role in drug release from sustained release polyester systems, therefore in order to elucidate the mechanism governing release, it appears essential to analyse the in vitro degradation behaviour of these devices. In this study the influence of processing conditions, particle characteristics and release media temperature on the degradation of PLGA spherical particles were examined. It was found that a linear relationship between the degradation rate and particle size existed, with the larger particles degrading fastest. In smaller particles degradation products formed within the particle can diffuse easily to the surface while in larger particles degradation products have a longer path to the surface of the particle during which autocatalytic degradation of the remaining polymer material can occur. The influence of release media temperature on the degradation of PLGA particles was also examined. At lower incubation temperatures PLGA microparticles showed an induction period after which polymer degradation proceeded. The rate of polymer degradation was found to increase with increasing incubation temperature. The polymer erosion profile was fitted to the Prout-Tompkins equation and the rate constants were used to determine the activation energy of PLGA hydrolysis.

Hot Temperature↗

The adsorption characteristics of heavy metals by various particle sizes of MSWI bottom ash.

The incineration rate of municipal solid waste (MSW) has been increased because of difficulty in securing a proper disposal site for MSW in Korea. The advantage of incineration is reduction of the volume of waste; however, significant amounts of bottom ash and fly ash were generated in the incineration process. Their treatment has attracted growing interest because of the potential toxicity of hazardous heavy metals. Generally, heavy metals are less released from bottom ash than from fly ash. In this study the adsorption characteristics of heavy metals were investigated using various particle sizes of MSWI bottom ash. Since bottom ash has a broad particle size distribution, it was sieved to size classes of +20, -20, -48, -80, -100 mesh. Cation exchange capacity (CEC) was analyzed by the ammonium acetate method to evaluate the potential as an adsorbent. The CEC values and surface areas increase as the range of particle size becomes finer. The adsorption experiment was conducted using synthetic (Cu and Ni) and plating rinse water as a function of reaction time (10-180 min), liquid/solid ratio (2-100) and particle size (+20 to -100 mesh), respectively. The adsorption rate increased with decreasing particle size and with increasing liquid/solid ratio; however, the removal efficiency of Cu was higher than that of Ni. In the case of plating rinse water, the adsorption rate decreased sharply at high liquid/solid ratio, and it showed over 80% of adsorption rates for Cu and Ni at an initial pH of 3.

Adsorption↗

Can the organization of a binary mix be predicted from the surface energy, cohesion parameter and particle size of its components?

PURPOSE: The aim of this study was to relate the organization of several binary mixes with three physical parameters (surface energy, cohesion parameter, and particle size) of various materials blended with each other. METHODS: Four pharmaceutical compounds were selected for their surface energies and cohesion parameters. Binary mixes were prepared from different sieved fractions. The frequency and nature of the interactions between the particles were observed by scanning electron microscopy. RESULTS: As expected, interactions were determined by both the energetics and the relative particle size of the two compounds blended, the latter determining the mode of interaction. However, particle size was not the only factor influencing the organization of the blends as, sometimes, small particles of a material would not adhere to the coarser particles of the other. Thus, a surface energy derived parameter ¿(B/A)lambda - (A/B)lambda¿ appears to be a valuable estimating tool of the potentiality of interaction between the particles blended. No correlation between the cohesion parameters of the compounds and the organization of the resulting blends could be found. CONCLUSIONS: Surface energy and particle size play a major role in the organization of a binary blend. However, they cannot explain separately the interactions observed between the fractions blended as reliable predictions require the use of both characteristics.

Adhesiveness↗

Determination by photon correlation spectroscopy of particle size distributions in lipid vesicle suspensions.

A method of determining particle size distributions in lipid vesicle preparations is outlined. A vesicle suspension is modeled as a polydisperse mixture of spherical shells. The distribution of particle sizes in this mixture is approximated by a continuous, piecewise linear function called a first-order spline. Excellent simultaneous fits to photon correlation spectroscopy data gathered at several different angles are presented. An error analysis is included to indicate the resolution of the method.

Light↗

HDL particle size: a marker of the gender difference in the metabolic risk profile.

A low plasma HDL-cholesterol concentration is an important risk factor for coronary heart disease (CHD) and is often accompanied by increased triglyceride concentrations. Women have generally higher HDL-cholesterol and lower triglyceride concentrations and concomitantly are at lower risk of CHD than men. As HDL particle size is a new and potentially important marker of CHD risk, we have examined the potential gender difference in HDL particle size, assessed by nondenaturing 4-30% polyacrylamide gradient gel electrophoresis, in a sample of men (n=231) and women (n=183). Overall, men were characterized by a less favorable lipoprotein--lipid profile, which was accompanied by smaller HDL particle size compared to women. However, when men and women were matched for HDL particle size and compared for their metabolic profile, it was found that both genders were characterized by similar plasma lipoprotein--lipid profile despite the fact that women were characterized by higher levels of total body fat but lower waist girth than men. In summary, HDL particle size is a strong marker of the gender-related difference in the determination of the metabolic risk profile.

Adolescent↗

Effect of particle size reduction on dissolution and oral absorption of a poorly water-soluble drug, cilostazol, in beagle dogs.

The purpose of the present study was to investigate the effects of particle size on the dissolution and oral absorption of cilostazol. Three types of suspensions having different particle size distributions were prepared of the hammer-milled, the jet-milled cilostazol crystals and the NanoCrystal spray-dried powder of cilostazol. In vitro dissolution rate of cilostazol was significantly increased by reducing the particle size. The dissolution curves of the cilostazol suspensions were in good agreement with the simulation based on the Noyes-Whitney equation. The bioavailability of cilostazol after oral administration to dogs was increased with reducing the particle size. While positive food effect on the absorption was observed for the suspensions made of the hammer-milled and the jet-milled crystals, no significant food effect was found for the suspension made of the NanoCrystal cilostazol spray-dried powder. These results could be qualitatively predicted from the in vitro dissolution data using the bio-relevant media, FaSSIF and FeSSIF. In conclusion, the NanoCrystal technology is found to be efficient to improve the oral bioavailability of cilostazol and to avoid the food effect on the absorption.

Administration, Oral↗

Effects of variety and particle size upon utilization of fescue hay by lactating dairy cows and dairy heifers.

Missouri-96 and Kentucky-31 hays were chopped with a tub grinder containing screens with apertures of 31, 63, or 100 mm in diameter and fed to dairy cows or heifers. Particle sizes (geometric mean diameter) were 1218, 1486, and 1933 micron, respectively, for the 31, 63, and 100-mm treatments. In Trial 1, the six treatments were fed ad libitum to 24 lactating cows; concentrate was offered at 1 kg/2 kg of milk. Dry matter intake and NDF digestibility were greater for Kentucky-31, but there were no other effects of variety. Particle size did not affect DM intake, DM or fiber digestibility, nitrogen partition, milk yield, or milk fat percentage. Crude protein digestibility was greatest for the 63-mm particle size treatment. In trial 2, the six treatments were fed ad libitum to 24 dairy heifers. Intake was greater for the 31 than for the 100-mm treatment but was unaffected by variety. Variety and particle size did not affect DM digestibility, nitrogen utilization, or daily gain. In this study fescue hay chopped through screens having apertures ranging from 31 to 100 mm was without effect on milk yield or composition. Reducing particle size increased intake and nitrogen utilization but not DM or fiber digestibility.

Animal Feed↗

Adsorption of proteins on Sepharose affinity adsorbents of varying particle size.

The binding of bovine serum albumin (BSA) and lysozyme to a series of samples of Cibacron Blue F3G-A Sepharose CL-6B with different narrow-range mean particle diameters has been investigated. Significant variation with particle size has been found for the parameters measured. For both proteins the maximum capacities obtained increased with decreasing particle size. For lysozyme, this percentage increase in capacity is less than the percentage increase in external surface area as the particle size decreases. For BSA, however, the percentage increase in capacity is more than four times the increase in surface area. The dissociation constants and forward rate constants describing the affinity interaction also differ with particle size. Again the effects are more pronounced for the larger protein, BSA, than for lysozyme. The effect of these differing parameters on the performance of fixed beds has been assessed using a computer simulation of the adsorption process.

Adsorption↗

Direct estimation of the in vivo dissolution of spironolactone, in two particle size ranges, using the single-pass perfusion technique (Loc-I-Gut) in humans.

AIM: The objective of this in vivo dissolution study was to investigate the usefulness of the Loc-I-Gut technique for differentiating between the in vivo dissolution rate of two particle sizes of spironolactone, and to compare these in vivo results with corresponding in vitro data. METHODS: The study included six volunteers, and consisted of three sequential parts (I, II, III). In parts I and III the in vivo dissolution was measured directly by perfusing a semi-open segment in the proximal jejunum. In part II, a solution of spironolactone was administered orally, and the plasma concentration time profile was followed for 48 h. The in vitro dissolution was measured using flow-through cells and different dissolution media simulating human gastrointestinal fluids. RESULTS: A difference in in vivo dissolution rate of the two different particle sizes was observed, based on perfusion data. This difference was not pronounced in the relative bioavailability of spironolactone administered in two different particle sizes. The relative bioavailability was dependent on the bile acid concentration in vivo. In vitro, dissolution rate of the smaller particles was improved at fasted state bile acid concentrations, while the larger particles were only significantly affected at fed state bile acid concentrations. CONCLUSION: In vivo dissolution studies discriminated between the dissolution rate of the two different particle sizes of spironolactone, based on the perfusate samples. The lack of difference in relative bioavailability, might be explained by the insufficient wash-out of particles after ending the perfusion, reabsorption of surface active ingredients along the GI tract, relatively small difference in particle size and the large inter- and intra-individual differences in pharmacokinetic variables.

Adsorption↗

LDL particle size and lipid composition are risk factors for microalbuminuria in normotensive and normocholesterolemic patients with type 2 diabetes.

The study was to evaluate the influence of particle size and lipid composition of low-density lipoprotein (LDL) on urinary albumin excretion and oxidative susceptibility of LDL, and to define association between LDL particle size and alpha-tocopherol content in LDL from normotensive and normocholesterolemic patients with type 2 diabetes. Twenty-three patients with type 2 diabetes (13 males, 10 females) were studied, and none of these patients had hypertension, hypercholesterolemia and overt proteinuria. The baseline body mass index of all patients was less than 28 kg/m2. All patients were hospitalized in Hirosaki University Hospital and took dietary therapy whose total intake was restricted to less than 30 kcal/kg of ideal body weight for 3 weeks. Their plasma glucose levels were controlled within fasting plasma glucose <140 mg/dl and 2-h postprandial plasma glucose <200 mg/dl. LDL particle size was evaluated by using high-resolution polyacrylamide gel electrophoresis (Lipoprint LDL System) and expressed by Rf value. LDL was incubated with 0.25 microM CuSO4 for 20 h, and the degree of LDL oxidation was determined by malondialdehide analysis. Twenty-four-hour urinary C-peptide excretion and plasma triglyceride concentration in patients with microalbuminuria were significantly higher than those in normoalbuminuric patients. Rf values in microalbuminuric patients were significantly greater than those in normoalbuminuric patients. There were significantly inverse correlations between Rf value and alpha-tocopherol content in LDL, and between Rf value and LDL-free cholesterol/LDL-total cholesterol. Thiobarbituarte-reactive substance level in LDL had a tendency to correlate with Rf value and significantly inverse correlation to alpha-tocopherol content in LDL. In type 2 diabetics without hypertension, hypercholesterolemia and obvious obesity, smaller LDL particle size, accompanied by mild hyperinsulinemia and mild hypertriglyceridemia seems to be one of the important factors responsible for microalbuminuria. In addition, the present study suggests that the decrease of alpha-tocopherol content in small LDL particle is associated with oxidative susceptibility to Cu2+-induced oxidation.

Aged↗

Fasting plasma insulin modulates lipid levels and particle sizes in 2- to 3-year-old children.

OBJECTIVE: Obesity and hyperinsulinemia are associated with dyslipidemia in adults and older children, but little is known about these relationships in very young children. We examined the relation of fasting insulin to lipid levels and lipid particle size in young healthy children. RESEARCH METHODS AND PROCEDURES: Analyses were performed on data from 491 healthy 2- and 3-year old Hispanic children enrolled in a dietary study conducted in New York City, 1992-1995. Obesity measures included BMI, ponderal index, skinfold thickness, and waist circumference. Low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol particle size were measured by nuclear magnetic resonance. RESULTS: Fasting insulin level was positively correlated with triglyceride levels (r = 0.24 for boys and r = 0.23 for girls; p < 0.001 for both) and inversely correlated with HDL-cholesterol level in boys (r = -0.20; p < 0.01). Higher fasting insulin level was also correlated with smaller mean HDL particle size in both boys (r = -0.21; p < 0.001) and girls (r = -0.14; p < 0.05) and smaller mean LDL particle size in boys (r = -0.13; p < 0.05). The associations of fasting insulin level with triglyceride and HDL-cholesterol levels and HDL and LDL particle size remained significant after multivariate regression adjustment for age, sex, and BMI or ponderal index. DISCUSSION: Fasting insulin level is associated with relative dyslipidemia in healthy 2- and 3-year-old Hispanic children.

Body Mass Index↗

Influence of single versus multiple actuations on the particle size distribution of beclometasone dipropionate metered-dose inhalers.

The particle size distributions of beclometasone dipropionate delivered from Becotide and Respocort inhalers after single and multiple actuations were investigated using the Andersen Mark II Cascade impactor and the drug was quantified using high performance liquid chromatography. The fine particle mass and the mass median aerodynamic diameter were calculated. An apparent increase in mass median aerodynamic diameter was observed when the number of actuations increased. In addition, the fine particle mass decreased as the number of actuations increased. When performing and analysing cascade impaction study data differences between single versus multiple actuations must be considered. Regulatory guidelines should be amended to stipulate the number of actuations to be loaded into devices used to evaluate the particle size distribution of inhaled aerosol products.

Administration, Intranasal↗

Determination of particle size for airborne UO2 dust at a fuel fabrication work station and its implication on the derivation and use of ICRP Publication 30 derived air concentration values.

When internal radiation exposure occurs via the inhalation route, the activity deposition in the respiratory tract is dependent on the particle size distribution of the radioactive aerosol. This fact has been recognized by ICRP Publication 30 in which annual limit of intake (ALI) and derived air concentration (DAC) values have been calculated for a variety of radionuclides based upon an activity median aerodynamic diameter (AMAD) of 1 micron. When radioactive aerosols have AMADs not equal to 1 micron, ICRP Publication 30 suggests the use of correction factors to calculate the appropriate ALI and DAC values. This work describes the measurement of particle size distribution for UO2 dust at a fuel fabrication work station by means of a cascade impactor. Measurements were made on 39 d spread over a 10-mo period to determine if the particle size distribution was stable over a year. The results of this study indicate that for this work station the measured AMAD values are not stable over a year. A discussion is provided on the treatment of such particle-size distribution data with the objective of extracting a representative particle-size distribution value, upon which an ALI and a DAC value can be determined. The observations made in this study have implications on the application of ICRP Publication 30 recommendations to operational health physics practice.

Air Pollutants↗

Particle size of roasted soybeans and the effect on milk production of dairy cows.

Fifteen cows were used in an experiment with a 5 x 5 replicated Latin square design to quantify the effect of particle size of roasted soybeans on milk production and fecal excretion of soybeans. The five experimental periods were each 2 wk long. Diets contained (percentage of dry matter) 33% alfalfa silage, 17% corn silage, 30.6% high moisture ear corn, 18% soybeans, and 1.4% mineral supplement. The five dietary treatments included raw whole soybeans or roasted soybeans in four particle sizes (whole and half, half and quarter, quarter and smaller, and coarsely ground). Mean particle sizes of the raw soybeans and of the roasted soybeans in whole and half sizes were > 4.75 mm. Mean particle sizes of the roasted soybeans in half and quarter, quarter and smaller, and coarsely ground roasted soybeans were 2.92, 2.01, and 1.59, respectively. During the normal handling of roasted soybeans, a large number of seeds was broken into halves in the treatment with whole and half sizes (36%, wt/wt basis). Production of 3.5% fat-corrected milk was 35.4, 37.7, 37.2, 35.1, and 35.4 kg/d for cows fed raw soybeans; roasted soybeans in whole and half, half and quarter, and quarter and smaller sizes; and ground roasted soybeans, respectively. Cows that were fed raw soybeans excreted the largest amount of visible soybean particles in feces, and cows that were fed ground roasted soybeans had the least amount of soybeans in the feces (61.3 vs. 10.6 g of soybeans/kg of fecal dry matter). Roasted soybeans in half and quarter sizes are optimal for milk production.

Animal Feed↗

Assessing the effect of latex particle size and distribution on the rheological and adhesive properties of model waterborne acrylic pressure-sensitive adhesives films.

The adhesive and rheological properties of model acrylic pressure-sensitive adhesive (PSA) films prepared from high solid emulsions with different particle sizes and distributions have been investigated with a customized probe tack apparatus. For each emulsion, the monomer composition and gel content were kept constant but different average particle sizes and distributions were used. Adhesive films 100 microm thick were then prepared from these emulsions and their rheological properties in the linear regime and adhesive properties were systematically characterized. Surprisingly, both the rheological and adhesive properties were found to be very dependent on the initial latex particle size distribution. A series of experiments were carried out to assess the adhesive properties of films made from blends of small- and large-particle-size latexes. Using the probe tack test, a maximum in adhesion energy of the dry films was found for 60% of small particles in the blend, a composition clearly different from that giving a minimum viscosity of the latex implying that optimizing for properties may not be equivalent to optimizing for processing in these adhesive applications. Finally, the adhesive properties of two multimodal latexes with different particle size distributions were investigated. Both gave significantly higher adhesion energies and clear evidence of a fibrillar detachment process. This important result suggests that the spatial distribution of gel domains in the dry film and the molecular connectivity between those gel domains also play an important role in controlling its adhesive properties.

Journal Article↗